Development of standardized extractive solution from Lippia sidoides by factorial design and their redox active profile

AbstractThe aim of this study was to evaluate the influences of variables of preparation on total flavonoids content from extractive solution of Lippia sidoides Cham., Verbenaceae. Thus a 23 factorial design was used to study the importance of plant proportion, the extraction method and solvent on the extraction of flavonoid. The methodology of determination of chemicals in factorial design was validated according to the parameters required by Brazilian Health Agency. The extraction solution was selected through a full factorial design where the best conditions to achieve the highest content of flavonoids were: 7.5% (w/v) of plant with ethanol 50% (v/v) as solvent. The polyphenols content was determined by LC method and its relationship with the antioxidant and free radical scavenging activities was evaluated. The free radical scavenging activities and antioxidant potentials were determined for different concentrations using various in vitro models. Our results indicate that extracts exhibited a significant dose-dependent antioxidant effect as evaluated by TRAP/TAR assays. Besides, we observed an antioxidant activity against hydroxyl radicals and nitric oxide, and protection against lipid peroxidation in vitro. Our results suggest that the extract presents significant in vitro antioxidant potential indicating promising perspectives for its use as pharmaceutical/or food additive.

Hyptis pectinata gel prevents alveolar bone resorption in experimental periodontitis in rats

Hyptis pectinata (L.) Poit., Lamiaceae, is an aromatic, abundant and broadly used plant species in Sergipe to treat oral and gastrointestinal pain and inflammation. The aim of the present study was to analyze the relation between periodontitis and changes in the corporal mass and alveolar bone structure after induction of experimental periodontal disease in rat treated or not treated with H. pectinata gel at 5% (GS5%) and 10% (GS10%), comparing their effects with doxycycline gel at 10% (D10%, positive control), vehicle gel (negative control) and a group with experimental periodontal disease, but non-treated. The gels were locally applied in the gingival region immediately after the experimental periodontal disease induction by ligature (3×/day, 11 days). Bone destruction was determined through clinical exam, histopathological analysis and cone beam computed tomography of the experimental animals (n = 36). After 11 days of periodontitis induction, all groups that received ligature presented a decrease in the corporal mass, except to the naïve group (without experimental periodontal disease) (p < 0.05). Computed tomography results have shown healthy bone structure in the group I and bone resorption for the test groups. Histopathological analysis confirmed the healthy bone structure for naïve group animals, while the test groups exhibited bone loss in several degrees. In particular, the non-treated group animals had an intense inflammatory process. When the periodontium of the animals treated with GS10% was histopathologically analyzed, insertion periodontium was preserved. The results for these groups were significantly different of the vehicle group (p < 0.05). According to the results, the gel based in the aqueous extract of H. pectinata at 10% can prevent bone loss in experimental periodontal disease similarly to doxycycline 10%.

Evaluation of wound healing activity of atranorin, a lichen secondary metabolite, on rodents

The aim of this study was to investigate the wound healing activity of atranorin cream (Patent requested) on excision wounds. Seventy-two male rats were anesthetized and an excisional wound was performed. Then the rats were randomly assigned into three groups: untreated control group; atranorin 1 (group treated with 1% AT ointment); and atranorin 5 (group treated with 5% AT ointment). Six animals of each group were euthanized 3, 7, 14 or 21 days after surgical procedures and the wounded areas were analyzed and removed. Serial histological sections were obtained and stained by histochemical techniques (Hematoxilin-Eosin-HEand Sirius red) and immunohistochemical techniques. Topical application of atranorin reduced wound areas, induced earlier granulation tissue formation, increased cell proliferation, improved collagenization and modulated the myofibroblasts differentiation when compared to control animals. It is suggested that atranorin modulates the wound healing process. These data suggest that this formulation based on atranorin extracted from Cladina kalbii AHTI may be a new biotechnological product for wound healing clinical applications.

Phytochemical screening, antinociceptive and anti-inflammatory activities of Chrysopogon zizanioides essential oil

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

p-Cymene reduces orofacial nociceptive response in mice

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2 percent Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

Bioassay-guided evaluation of central nervous system effects of citronellal in rodents

The central nervous system (CNS) depressant and anticonvulsant activities of citronellal (CT) were investigated in animal models. The CT in doses of 100, 200 and 400 mg/kg injected by i.p. route in mice caused a significant decrease in the motor activity of animals when compared with the control group. The highest dose of CT significantly reduced the remaining time of the animals on the Rota-rod apparatus up to 2 h. Additionally, CT at doses 100, 200 and 400 mg/ kg (i.p.) was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). It was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200 and 400 mg/kg, resulting in 30 and 40 percent of protection, respectively. This compound was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 400 mg/kg. In the same way, the anticonvulsant effect of CT was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities.

Assessment of antinociceptive and anti-inflammatory activities of Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract

The present work investigated the antinociceptive and antiinflammatory activities of the Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract (PRAE). For this purpose, acetic acid writhing, paw licking induced by formalin, hot-plate and pleurisy tests were performed. The doses of 100, 200 and 400 mg/kg (p.o.) significantly inhibited the writhing 63.4, 89.6 and 94.8 percent, respectively, in comparison with control group. The lick of the paw 1st phase was reduced at the dose of 400 mg/ kg (24.9 percent), while the 2nd phase had reduction at doses 200 and 400 mg/ kg (23.1 and 34.4 percent), respectively. The PRAE inhibited the carrageenaninduced neutrophil migration to the peritoneal cavity in a higher dose (p<0.05). Taken together, our results suggest that the PRAE can constitute target potential for use in therapies of the pain and inflammation.

Citral reduces nociceptive and inflammatory response in rodents

Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8 percent) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

Anticonvulsant property of N-salicyloyltryptamine: evidence of enhance of central GABAergic neurotransmission / Propriedade anticonvulsivante de N-saliciloiltriptamina: proteção significativa com o sistema GABAérgico

AIM: In the present study we verified the anticonvulsant properties of the new tryptamine analogue, N-salicyloyltryptamine (NST), in rodents. METHODS AND RESULTS: In the evaluation of the anticonvulsant activity, NST protected the animals from the incidence of seizures induced by pentylenetetrazole (PTZ) and picrotoxin (PIC), in doses of 100 and 200 mg/kg. NST (100 and 200 mg/kg, i.p.) significantly eliminated the extensor reflex of maximal electric-induced seizure tests in 40 percent of the experimental animals. However, in the PTZ model FLU (10 mg/kg, i.p.), an antagonist of the benzodiazepine (BZD) site in the GABA A-BZD receptor complex, inhibited the prolongation of seizure latency induced by NST. CONCLUSION: Our results demonstrated an anticonvulsant activity of the new analogue that could be, at least in part, associated to the involvement of the GABAergic mechanism.

OBJETIVO: O presente estudo buscou avaliar o possível efeito anticonvulsivante do novo análogo da triptamina, N-saliciloiltriptamina (NST), em roedores. MÉTODOS E RESULTADOS: Na avaliação do efeito anticonvulsivante, os animais tratados com NST (100 e 200 mg/kg, i.p.) foram protegidos de maneira estatisticamente significativa (p<0,05) quanto a latência e incidência do aparecimento das convulsões induzidas pela administração do pentilenotetrazol (PTZ) e da picrotoxina (PIC). O efeito protetor do NST nas convulsões induzidas pelo PTZ foi revertido pela administração do flumazenil (10 mg/kg, i.p.), um antagonista dos receptores GABA-benzodiazepínicos (GABA A-BZD). A administração de NST (100 e 200 mg/kg, i.p.) protegeu de forma estatisticamente significativa (p < 0,05) os animais no teste das convulsões induzidas pelo eletrochoque-auricular em camundongos. CONCLUSÃO: Os resultados do presente estudo sugerem que o efeito anticonvulsivante de NST está associado, pelo menos em parte, ao sistema GABAérgico.

Desenvolvimento do algoritmo de classificação hierárquica (Winclus) e aplicação à série de derivados indol-2-carboxilato / Development of a Hierarquical Classification Algorithm (Winclus) and its application to a indole-2-carboxylate series

A Classificação Hierárquica ou Cluster Analysis é um tipo de reconhecimento de padrões aplicável ao planejamento de fármacos. Nesse trabalho, apresenta-se um modelo de classificação aglomerativa, de forma a agrupar substituintes com base nas similaridades dos seus parâmetros físico-químicos. Uma vez agrupados, estuda-se a relação entre o modelo de classificação hierárquica e as respostas biológicas dos compostos, a partir da Relação Quantitativa Estrutura-Atividade (QSAR). O método é representado por um novo algoritmo, denominado Winclus, para o qual foi desenvolvido um programa destinado à sua aplicação. Neste trabalho, é abordo o desenvolvimento do software e a aplicação do mesmo à série...